Electron microscopy of an alpha-dystroglycan fragment containing receptor sites for lymphocytic choriomeningitis virus and laminin, and use of the receptoid body as a reagent to neutralize virus

Virology. 2004 Aug 1;325(2):207-15. doi: 10.1016/j.virol.2004.04.044.

Abstract

We report the electron microscopic structure of an alpha-dystroglycan (alpha-DG) fragment (DGEKFc4) that contains binding sites for lymphocytic choriomeningitis virus (LCMV) and the extracellular matrix (ECM) molecule laminin. In electron microscopic images, DGEKFc4 appears as dumbbell-shaped rods with a length of 7.5 +/- 0.5 nM and width of 3 +/- 0.3 nM. The C-terminal human Fc allows binding of anti-human Fc antibody resulting in formation of immune complexes that preserve alpha-DG binding to virus. Electron microscopy shows the antibody binding to near one end of the dumbbell-shaped rods. Because arenaviruses like LCMV or Lassa fever virus (LFV) generate poor neutralizing antibodies during natural infection or vaccination, we assayed whether the alpha-DG receptoid bodies generated could be used as an efficient antibody mimic. However, the receptor body formed by either alpha-DG fragment alone or complexed to antibody to human Fc failed to efficiently neutralize virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology
  • Cytoskeletal Proteins / ultrastructure*
  • DNA Primers / genetics
  • Dystroglycans
  • Humans
  • In Vitro Techniques
  • Lymphocytic choriomeningitis virus / physiology*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Membrane Glycoproteins / ultrastructure*
  • Microscopy, Electron
  • Neutralization Tests
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology
  • Peptide Fragments / ultrastructure*
  • Rabbits
  • Receptors, Laminin / physiology
  • Receptors, Virus / physiology

Substances

  • Cytoskeletal Proteins
  • DAG1 protein, human
  • DNA Primers
  • Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Laminin
  • Receptors, Virus
  • Dystroglycans